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Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.
Brouwer, Philip J M; Antanasijevic, Aleksandar; Ronk, Adam J; Müller-Kräuter, Helena; Watanabe, Yasunori; Claireaux, Mathieu; Perrett, Hailee R; Bijl, Tom P L; Grobben, Marloes; Umotoy, Jeffrey C; Schriek, Angela I; Burger, Judith A; Tejjani, Khadija; Lloyd, Nicole M; Steijaert, Thijs H; van Haaren, Marlies M; Sliepen, Kwinten; de Taeye, Steven W; van Gils, Marit J; Crispin, Max; Strecker, Thomas; Bukreyev, Alexander; Ward, Andrew B; Sanders, Rogier W.
Afiliação
  • Brouwer PJM; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands; Department of Integrative, Structural and Computational Biology, The Scripps Res
  • Antanasijevic A; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ronk AJ; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77550, USA; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA.
  • Müller-Kräuter H; Institute of Virology, Philipps University Marburg, 35043 Marburg, Germany.
  • Watanabe Y; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
  • Claireaux M; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Perrett HR; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Bijl TPL; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Grobben M; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Umotoy JC; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Schriek AI; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Burger JA; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Tejjani K; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Lloyd NM; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77550, USA; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA.
  • Steijaert TH; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • van Haaren MM; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Sliepen K; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • de Taeye SW; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • van Gils MJ; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands.
  • Crispin M; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
  • Strecker T; Institute of Virology, Philipps University Marburg, 35043 Marburg, Germany.
  • Bukreyev A; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77550, USA; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77550, USA.
  • Ward AB; Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: andrew@scripps.edu.
  • Sanders RW; Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell Univ
Cell Host Microbe ; 30(12): 1759-1772.e12, 2022 12 14.
Article em En | MEDLINE | ID: mdl-36400021
The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nanopartículas / Febre Lassa Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nanopartículas / Febre Lassa Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article